Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants: A Review of the Clinical Effectiveness

Transcription

1 CADTH RAPID RESPONSE REPORT: SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants: A Review of the Clinical Effectiveness Service Line: Rapid Response Service Version: 1.0 Publication Date: July 4, 2017 Report Length: 27 Pages

2 Authors: Khai Tran, Charlene Argáez Cite As: Smoking reduction and cessation interventions for pregnant women and mothers of infants. Ottawa: CADTH; 2017 Jul. (CADTH rapid response report: summary with critical appraisal). Acknowledgments: ISSN: (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services. While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH. CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the contents of this document or any of the source materials. This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites. Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada s federal, provincial, or territorial governments or any third party supplier of information. This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user s own risk. This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada. The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors. About CADTH: CADTH is an independent, not-for-profit organization responsible for providing Canada s health care decision-makers with objective evidence to help make informed decisions about the optimal use of drugs, medical devices, diagnostics, and procedures in our health care system. SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 2

3 Context and Policy Issues Cigarette smoking during pregnancy can result in serious health risks for pregnant women and their infants. 1 Nicotine, carbon monoxide, and other chemicals in the tobacco smoke can cause cancer, still births, preterm births, low birthweight, miscarriages, prenatal deaths, and sudden infant death syndrome. 1 In Canada, the prevalence of smoking among pregnant women dropped from 17% in 2000/2001 to 10.5% in 2005/2006, 2 and pregnant mothers consumed an average of seven cigarettes per day. 2 Smoking rates during pregnancy were most prevalent in the Northern Territories (39.4%) and Prince Edward Island (20.8%) compared to the rest of Canada. 2 The prevalence of smoking during pregnancy was higher in women, who were younger than 25 years old, unmarried, limited education, low income, non-immigrants, and poor in overall health. 3 Many different pharmacological (e.g., nicotine replacement therapy [NRT], bupropion and varenicline) and non-pharmacological interventions (e.g., behavioral therapy), given alone or in combination, were effective in helping the adult population to stop smoking. 4 Despite an effective smoking cessation profile in the general population, evidence regarding the use of these interventions in pregnant women is less clear. Furthermore, it is uncertain whether there exists a program that is effective in helping pregnant women, who have difficulty to stop smoking, to change their smoking behaviour (i.e., reduce the number of cigarettes smoked per day). The aim of this report is to review the clinical effectiveness of smoking reduction programs and smoking cessation interventions for pregnant women and mothers of infants. Research Questions 1. What is the clinical effectiveness of smoking reduction programs for pregnant women or mothers of infants? 2. What is the clinical effectiveness of smoking cessation interventions for pregnant women or mothers of infants? Key Findings Evidence on the effectiveness of smoking reduction interventions was limited. Psychosocial interventions for smoking cessation appeared to be effective, while the effect of health education and social support was less certain. The results suggested that psychosocial interventions reduced the risk of infants born with low birthweight, increased the mean birthweight, and decreased the risk of neonatal intensive care unit admission. Pharmacological interventions appeared to be effective during treatment or at the end of pregnancy. Nicotine replacement therapy did not seem to have any positive or negative effects on infant outcomes, while the safety of bupropion was inconclusive. SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 3

4 Table 1: Selection Criteria Population Intervention Comparator Outcomes Study Designs Methods Literature Search Methods A limited literature search was conducted on key resources including PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. Filters were applied to limit the retrieval to health technology assessments, systematic reviews, meta-analyses, non-randomized studies, and randomized controlled trials. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2012 and June 6, Selection Criteria and Methods One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1. Women who smoke and who are pregnant, new mothers or mothers of infants, breastfeeding Q1: Smoking reduction interventions Q2: Smoking cessation interventions - pharmacologic (e.g., nicotine replacement therapy) or non-pharmacologic (e.g. behavioural) Any comparator (another intervention or without intervention) Effectiveness, success, risks, complications, safety (e.g., preventing low/very low birth weight, premature birth, infant mortality, fetal growth retardation, respiratory complications, behavioural disorders, apgar scores, maternal anemia, placental abruption) Health technology assessments (HTAs), systematic reviews (SRs), meta-analyses (MAs), randomized controlled trials (RCTs) or non-randomized studies Exclusion Criteria Studies were excluded if they did not satisfy the selection criteria in Table 1, and if they were published prior to Conference abstracts, duplicates of publication of the same, or systematic reviews (SRs), in which their included studies were overlapped with another SR published at a later date, were excluded. Non-randomized studies were excluded if SRs of randomized controlled trials (RCTs) or recently published RCTs were found. Critical Appraisal of Individual Studies The SIGN checklists were used to assess the quality of SRs and MAs, 5 and RCTs. 6 SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 4

5 Summary of Evidence Quantity of Research Available A total of 492 citations were identified in the literature search. Following screening of titles and abstracts, 443 citations were excluded and 49 potentially relevant reports from the electronic search were retrieved for full-text review. Two potentially relevant publications were retrieved from the grey literature search. Of these potentially relevant articles, 44 publications were excluded for various reasons, while seven publications, including two SRs and five RCTs, met the inclusion criteria and were included in this report. Appendix 1 describes the PRISMA flowchart of the selection. Summary of Study Characteristics The characteristics of the SRs and MAs 7,8 and RCTs 9-13 are summarized below and are presented in Appendix 2. SRs and MAs Study Design One SR 7 included 88 RCTs with 106 arms involving over 26,000 pregnant smokers and provided data on psychosocial interventions to support pregnant women to stop smoking. Another SR 8 included nine RCTs (eight trials with NRT and one trial with bupropion) on pharmacological interventions for promoting smoking cessation during pregnancy of 2,210 pregnant smokers. Country of Origin Both SRs were conducted by authors from the United Kingdom (UK) 7,8 and were published in and Population The overall populations of the included trials in both SRs 7,8 were in the first or second trimester of pregnancy. Most were healthy women of 16 years or older, with different ethnic backgrounds, education, and socioeconomic status. 7,8 The gestational age ranged from 9 to less than 30 weeks. 8 Interventions and Comparators The psychosocial interventions were categorized as counselling (54 trials), health education (12 trials), feedback (6 trials), incentives (13 trials), social support (7 trials) and exercise (1 trial). 7 These interventions were compared with usual care, a less intensive intervention, or an alternative intervention. 7 The pharmacological interventions included NRT (8 trials) and bupropion (1 trial) as an adjunct to behavioral support. 8 Transdermal nicotine patches were mostly used as an intervention in NRT compared to gum and lozenge. The comparators were either placebo or behavioral support alone. Outcomes The primary outcomes in both SRs 7,8 were smoking abstinence rates that were biochemically validated. The secondary outcomes included continued abstinence after childbirth, 7 smoking reduction in late pregnancy, 7 infant outcomes 7,8 and adverse effects. 7,8 The infant outcomes included low birthweight (under 2,500 g), 7,8 very low birthweight (under 1,500 g), 7 preterm birth (under 37 weeks), 7,8 mean birthweight, 7,8 stillbirth, 7,8 perinatal SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 5

6 death, 7,8 neonatal death, 7 neonatal intensive care unit admissions, 7 and congenital abnormalities. 8 Follow-up Period The follow-up periods in the trials included in both SRs 7,8 were conducted during pregnancy and up to two years after childbirth. Data Analysis and Synthesis Meta-analyses were conducted to synthesize data in the both SRs. 7,8 Both clinical and statistical heterogeneity were considered by performing subgroup analyses, metaregressions, or sensitivity analyses. 7,8 Quality Appraisal The Cochrane risk of bias tool was used to assess the methodological quality of included studies in both SRs. 7,8 The strength of evidence for each body of evidence was assessed using GRADE (the Grading of Recommendations Assessment, Development and Evaluation) approach in one SR. 7 RCTs Study Design Of the five included RCTs, one was active-controlled, 9 one was double-blind placebo controlled, 10 two were single-blinded, 11,13 and one was of a cluster design. 12 Three RCTs recruited patients from multiple centres, and two RCTs enrolled patients from a single centre. 9,10 Country of Origin The RCTs were conducted in the UK, 11 United States, 9,10 Argentina 12 and the Netherlands, 13 and were published in 2017, and Population All RCTs included pregnant smokers with a mean age ranging from to 26.5 years. 10 One RCT included negative affect pregnant smokers who had emotional issues, such as anxiety, dysthymia, anger, and stress. 9 One RCT included young pregnant women with low education levels. 13 The mean gestational age ranged from 15 9,11 to 20 weeks, 13 the average smoking at enrolment ranged from 8 9,13 to cigarettes per day. Interventions and Comparators The comparisons were emotional regulation treatment (ERT) versus health and lifestyle intervention (HLS), 9 self-help smoking cessation text message (MiQuit) versus usual care, 11 counselling (based on the 5As [Ask, Advise, Assess, Assist, and Arrange]) versus control, 12 nurse home visitations versus usual care, 13 and bupropion sustained release versus placebo. 10 The purpose of the nurse home visitations was to help reduce cigarette smoking and promote breastfeeding among young pregnant smokers. 13 SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 6

7 Outcomes The outcomes included biochemically validated smoking abstinence rates, 9-11 the number of cigarettes smoked per day, 9,13 continuous and quit smoking during pregnancy, 12 infant outcomes, 10,13 and maternal outcomes. 10 Follow-up Period The follow-up periods in the included RCTs were done both during pregnancy and up to four months after childbirth. Analysis The evaluations of endpoints in three RCTs were performed on an intention-totreat (ITT) basis, while the analysis in two RCTs 9,13 was performed on a per-protocol (PP) basis. Three RCTs presented a sample size calculation to obtain sufficient power for the primary outcome, and two RCTs 9,13 did not reported a sample size calculation. Summary of Critical Appraisal The summary of the quality assessment for the SRs and RCTs were briefly described below and are presented in Appendix 3. SRs and MAs The SRs 7,8 were of high quality as most of the criteria were fulfilled, including an explicit research question, a comprehensive literature search, and at least two people were independently involved in the selection and data extraction. Also, the publication status was not used as an inclusion criterion, and relevant characteristics, quality assessment of included studies and a declaration of the conflicts of interest were completed. Appropriate methods of meta-analysis were used to combine the individual findings. Publication bias was assessed in one SR, 7 and was not applicable in the other SR 8 as there were eight individual studies included. Both SRs provided a list of excluded studies. RCTs One RCT 10 was of high quality as all criteria were fulfilled, including an explicit question, a detailed description of methodology on randomization, adequate method of concealment, blinding. As well, there was similarity between treatment groups, relevant outcome measures, an ITT analysis was conducted, and the trial was multi-centric. Four RCTs 9,11-13 were of moderate quality as some criteria were partially reported or not fulfilled, such as the method of concealment, 9,11-13 blinding 9,11-13 and ITT analysis. 9,13 The percentages of dropouts before completion in both arms were 44% and 53% 9 and 49% and 43% 10 in two RCTs. 9,10 Summary of Findings The main findings and conclusions of the included SRs and RCTs are presented in Appendix 4. Question 1: What is the clinical effectiveness of smoking reduction programs for pregnant women or mothers of infants? SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 7

8 One trial 13 was identified that assessed a home visitation program by trained nurses to help young pregnant women with a low education level in reducing cigarette smoking and promoting breastfeeding. Percentage of smokers The percentages of smokers in both intervention and control groups were not significantly different at either 32 weeks of pregnancy (33% vs 35%) or at two months after childbirth (48% vs 65%). After conducting the last observation carried forward approach to correct for missing data, the percentages of smokers in the intervention group were significantly lower than those in the control group; 40% versus 48% at 32 weeks of pregnancy, and 49% versus 62% at two months after childbirth. Number of cigarettes smoked per day There was no difference in the number of cigarettes smoked per day between the intervention and control groups (2 versus 3 cigarettes) at 32 weeks of pregnancy, although the numbers of cigarettes smoked in both groups reduced compared to those at enrolment (7 versus 8 cigarettes). At two months after birth, women in the control group increased their daily cigarettes smoked as of at baseline (8 cigarettes), while women in the intervention group smoked an average of 4 cigarettes per day. Pregnancy outcomes Birth weight, gestational age, the prevalence of low birth weight (i.e., <2,500 g), and the prevalence of premature babies (i.e., <37 weeks) were similar in both groups. Breastfeeding Breastfeeding initiation was similar in both groups (82% versus 78%). The percentage of women, who continued to breastfeed at 6 months after childbirth, was higher than in the intervention group than in the control group (13% versus 6%). Question 2: What is the clinical effectiveness of smoking cessation interventions for pregnant women or mothers of infants? One SR 7 and three RCTs 9,11,12 were identified that reported relevant outcomes for the psychosocial interventions, and one SR 8 and one RCT 10 were identified that reported relevant outcomes for pharmacological interventions. Psychosocial Interventions Smoking abstinence in late pregnancy There was evidence from the SR 7 that counselling was more effective than usual care or less intensive intervention. It was uncertain about the effectiveness of counselling (i.e., cognitive behavioral therapy) compared with alternative intervention (i.e., health education or motivational interview). 7 There was uncertainty about the effectiveness of health education compared with usual care, less intensive intervention, or alternative interventions. 7 There was evidence that feedback significantly increased the rate of smoking cessation compared to usual care. 7 There was uncertainty if the feedback was more effective when compared to less intensive interventions. 7 SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 8

9 There was evidence that incentives significantly increased the rate of smoking cessation compared to alternative interventions. 7 However, it was uncertain about the effectiveness of incentives compared to usual care or less intensive interventions. 7 There was uncertainty on whether social support (i.e., peer or partner) increased the chance of smoking cessation when compared to less intensive interventions. 7 There was also uncertainty whether exercise increased the chance of smoking cessation when compared to usual care. 7 One RCT 12 showed that smoking cessation counselling based on the 5As had no difference in the frequency of women who smoked until the end of pregnancy compared to the control group. One RCT 9 showed that the emotional regulation treatment had a higher chance to stop smoking in negative affect pregnant smokers compared to health and lifestyle intervention, but the difference was not statistically significant. One RCT 11 showed that a test message intervention program may increase the abstinence rates of smoking compared to usual care, although the difference was not statistically significant. Continued abstinence (relapse prevention) in late pregnancy There was no evidence to suggest that counselling could prevent smoking relapse compared to usual care or less intensive interventions. 7 There was also uncertainty about the effectiveness of health education compared to usual care, or social support compared to less intensive interventions in smoking relapse prevention. 7 Continued abstinence in the postnatal period There was evidence that counselling increased the rate of smoking abstinence during postpartum periods (i.e., 0 to 5 months, 6 to 11 months and 12 to 17 months), compared to usual care. 7 However, there was uncertainty on whether counselling increased postpartum smoking abstinence compared to less intensive interventions or alternative interventions. 7 There was evidence that health education increased the rate smoking cessation in the early postpartum period (i.e., 0 to 5 months) compared to usual care or less intensive interventions. 7 There was evidence that incentives increased smoking abstinence during 6 to 11 months postpartum compared to usual care. 7 There was also evidence that incentives increased smoking abstinence at 0 to 5 months compared to less intensive interventions. 7 However, there was uncertainty if there was an increase in smoking cessation when incentives were compared to usual care at 0 to 5 months, or when incentives were compared to alternative interventions at 0 to 5 months or 6 to 11 months postpartum. 14 There was no evidence to suggest that social support was more effective than less intensive interventions, or exercise was more effective than usual care in promoting continued smoking abstinence during postnatal period. 7 Smoking reduction in late pregnancy It was uncertain on whether there were differences in smoking reduction that was biochemically validated in different comparisons including counselling versus usual care, counselling versus less intensive interventions, feedback versus usual care, incentives versus usual care, incentives versus alternative interventions, and social support versus less intensive interventions. 7 SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 9

10 Mean cigarettes smoked per day in late pregnancy There was evidence that health education, feedback and incentives significantly reduced the mean number of cigarettes smoked per day compared to usual care. 7 There was uncertainty that counselling and health education could decrease the number of cigarettes smoked per day compared to less intensive interventions. 7 Results from the included RCT 9 showed that emotion regulation treatment intervention given to a difficult-to-treat population did not significantly reduce the number of cigarettes smoked per day compared to a healthy lifestyle intervention. Infant outcomes Data from each of the infant outcomes were pooled from all interventions to increase the detection of rare events. 7 There was evidence that smoking cessation interventions reduced the risk of infants born with low birthweight (i.e., <2,500 g) by 17%, increased the mean birthweight by 55.6 g, and decreased the risk of neonatal intensive care unit (NICU) admission by 22%. 7 There was uncertainty whether there was any difference between smoking cessation interventions and controls with respect to the rates of very low birthweight (i.e., <1,500 g), preterm births (i.e., <37 weeks), stillbirths, perinatal deaths, and neonatal deaths. 7 Pharmacological Interventions Smoking abstinence in late pregnancy There was evidence that NRT increased the rates of biochemically validated smoking cessation by about 40% compared to the control group. 8 However, there was no difference in the self-reported smoking abstinence rates between NRT and the control group at 3, 6 or 12 months postpartum. Bupropion sustained release increased abstinence rates during treatment compared to placebo, but there was no significant difference in the abstinence rates between groups at the end of treatment, at the end of pregnancy, and during the postpartum period. 10 Mean cigarettes smoked per day in late pregnancy There was no significant difference in percent reduction in the number of cigarettes smoked per day between bupropion and placebo at the end of treatment, at the end of pregnancy, and during the postpartum period. 10 Infant outcomes There were no significant differences in all infant outcomes between NRT and control 8 or between bupropion and placebo. 10 Maternal outcomes There were no significant differences in body mass index, blood pressure, and pulse rate between bupropion and placebo. 10 Treatment side effects, such as headaches, difficulty sleeping, running nose, dry mouth, and anxiety, were similar in both groups. 10 SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 10

11 Limitations There was limited evidence on the clinical effectiveness of the smoking reduction programs for pregnant women or mothers of infants. One trial on smoking reduction program was identified that used self-reported questionnaires instead of biochemically assessments to measure cigarette smoking behavior of participants. The evidence on pharmacological interventions was derived from a SR published in 2015, has not been updated yet, and was limited to NRT only, with limited or no information on other medications. Given the difficulty in recruitment (i.e., 11 8 and participants) and the rate of early withdrawal (i.e., near 50% 10 ) from the bupropion trials, the effectiveness and safety of the medication were questionable. Conclusions and Implications for Decision or Policy Making There was limited evidence on the effectiveness of smoking reduction interventions, and it was unclear if a nurse home visitation program was effective in helping pregnant women to reduce smoking. There was strong to moderate evidence that suggested that psychosocial interventions for promoting smoking cessation during pregnancy can increase the proportion of women who stopped smoking in late pregnancy. Among the psychosocial interventions, counselling, feedback, and incentives appeared to be effective, while the effect of health education and social support was less certain. Counselling and incentives appeared to be effective for continued abstinence during the postpartum period. It was unclear if smoking cessation interventions can help pregnant women to reduce smoking. Pooled results suggested that psychosocial interventions reduced the risk of infants born with low birthweight, increased the mean birthweight, and decreased the risk of NICU admission. Pharmacological interventions, such as NRT and bupropion, appeared to be effective only during treatment or in late pregnancy, but not after pregnancy or during postpartum period. There was no evidence that NRT had any positive or negative effect on infant outcomes and the safety of bupropion was less clear. More evidence is needed, particularly, on the programs promoting smoking reduction for pregnant women, and on the effectiveness and safety of smoking cessation drugs, such as bupropion, varenicline, or other medications for pregnant smokers. SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 11

12 References 1. Pregnancy [Internet]. Ottawa: Health Canada; [cited 2017 Jun 21]. Available from: 2. Al-Sahab B, Saqib M, Hauser G, Tamim H. Prevalence of smoking during pregnancy and associated risk factors among Canadian women: a national survey. BMC Pregnancy Childbirth [Internet] May 24 [cited 2017 Jun 21];10:24. Available from: 3. Cui Y, Shooshtari S, Forget EL, Clara I, Cheung KF. Smoking during pregnancy: findings from the Canadian Community Health Survey. PLoS ONE [Internet] [cited 2017 Jun 21];9(1):e Available from: 4. Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral counseling and pharmacotherapy interventions for tobacco cessation in adults, including pregnant women: a review of reviews for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Sep. [cited 2017 Jun 9]. (U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews). Available from: pdf 5. Methodology checklist 1: systematic reviews and meta-analyses [Internet]. Edinburgh (GB): Scottish Intercollegiate Guidelines Network; 2007 [2017 Jun 9]. Available from: sign.ac.uk/assets/srchecklist.doc 6. Methodology checklist 2: controlled trials [Internet]. Edinburgh (GB): Scottish Intercollegiate Guidelines Network; [cited 2017 Jun 22]. Available from: 7. Chamberlain C, O'Mara-Eves A, Porter J, Coleman T, Perlen SM, Thomas J, et al. Psychosocial interventions for supporting women to stop smoking in pregnancy. Cochrane Database Syst Rev Feb 14;2:CD Coleman T, Chamberlain C, Davey MA, Cooper SE, Leonardi-Bee J. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev Dec 22;(12):CD Bradizza CM, Stasiewicz PR, Zhuo Y, Ruszczyk M, Maisto SA, Lucke JF, et al. Smoking cessation for pregnant smokers: development and pilot test of an emotion regulation treatment supplement to standard smoking cessation for negative affect smokers. Nicotine Tob Res May 1;19(5): Nanovskaya TN, Oncken C, Fokina VM, Feinn RS, Clark SM, West H, et al. Bupropion sustained release for pregnant smokers: a randomized, placebo-controlled trial. Am J Obstet Gynecol Apr;216(4): Naughton F, Cooper S, Foster K, Emery J, Leonardi-Bee J, Sutton S, et al. Large multi-centre pilot randomized controlled trial testing a low-cost, tailored, self-help smoking cessation text message intervention for pregnant smokers (MiQuit). Addiction Feb Althabe F, Aleman A, Berrueta M, Morello P, Gibbons L, Colomar M, et al. A multifaceted strategy to implement brief smoking cessation counseling during antenatal care in Argentina and Uruguay: a cluster randomized trial. Nicotine Tob Res [Internet] May [cited 2017 Jun 9];18(5): Available from: Mejdoubi J, van den Heijkant SC, van Leerdam FJ, Crone M, Crijnen A, HiraSing RA. Effects of nurse home visitation on cigarette smoking, pregnancy outcomes and breastfeeding: a randomized controlled trial. Midwifery Jun;30(6): Brouwers M, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. AGREE II: advancing guideline development, reporting and evaluation in healthcare. CMAJ [Internet] Dec;182(18):E839-E842. Available from: SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 12

13 Appendix 1: Selection of Included Studies 492 citations identified from electronic literature search and screened 443 citations excluded 49 potentially relevant articles retrieved for scrutiny (full text, if available) 2 potentially relevant reports retrieved from other sources (grey literature, hand search) 51 potentially relevant reports 44 reports excluded: Reviews (n=5) Overlapped SRs (n=8) RCTs included in SRs (n=13) Observational studies (n=11) Irrelevant outcomes (n=5) Irrelevant population (n=1) Irrelevant intervention (n=1) 7 reports included in review including 2 SRs, and 5 RCTs SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 13

14 Appendix 2: Characteristics of Included Studies Table A1: Characteristics of Included Systematic Reviews First Author, Publication Year, Country, Funding Chamberlain et al., Australia, UK Public Funding Types and Numbers of Primary Studies Included SR of 88 RCTs (n=106 arms) related to smoking cessation in late pregnancy. This was the sixth update review of the previous versions published in 1995, 1999, 2004, 2009 and 2013 Quality assessment using Cochrane risk of bias Population Characteristics Over 26,000 pregnant smokers, most were at first antenatal clinic visit and during the second trimester of pregnancy. Four trials had women who continued to smoke in late pregnancy Healthy pregnant women ( 16 years old, 23 trials) Low socioeconomic status ( 16 years old, 52 trials) Young women under 20 years (2 trials) Women with psychosocial risk factors (8 trials) Women required for methadone treatment for opioid addition (2 trials) Ethnic minority population (10 trials); indigenous communities (5 trials) Interventions Comparators Clinical Outcomes, Length of Follow-up Counselling (n=54) Health education (n=12) Feedback (n=6) Incentives (n=13) Social support (n=7) Exercise (n=1) Many interventions during pregnancy continued support into the postpartum period and measured postpartum outcomes. Interventions differed in intensity, duration and people involved in implementation Single intervention (n=57) Multiple intervention (n=36) Tailored intervention (n=12) Face-to-face counselling with different strategies (n=56) Counselling Usual care (n=56) Less intensive intervention (n=44) Alternative intervention (n=6) Primary outcomes Smoking abstinence (biochemically validated) Secondary outcomes Continued abstinence in the postnatal period 0 to 5 months Six to 11 months 2 to 17 months 14+ months Smoking reduction Infant outcomes Low birthweight Preterm births Mean birthweight Other perinatal outcomes Non pre-specified infant outcomes Breastfeeding Psychological effects Adverse effects Follow-up: during pregnancy and more than 14 months postnatal SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 14

15 First Author, Publication Year, Country, Funding Types and Numbers of Primary Studies Included Population Characteristics Interventions Comparators Clinical Outcomes, Length of Follow-up including lottery (n=4) Support from peers and/or partners (n=9) Duration and frequency generally increased overtime Coleman et al., Australia, UK Public Funding SR and MA of 9 RCTs (8 trials with NRT and 1 trial with bupropion) published between 2000 and 2015 Quality assessment using Cochrane risk of bias 2,210 pregnant smokers Age: 16 years old Gestational age: 9 to <30 weeks Smoking: 1 cigarette per day NRT (8 trials) and bupropion (1 trial) as adjuncts to behavioral support NRT: Nicotine gum (n=1) Nicotine patch (n=6) Choice of NRT formulations (n=1) Behavioral support Placebo Primary outcomes Smoking abstinence rates (biochemically validated) Secondary outcomes Abstinence from smoking after childbirth Safety Miscarriage or spontaneous abortion Stillbirth Mean unadjusted birthweight Low birthweight (<2,500 g) Preterm birth (<37 weeks) NICU admissions Neonatal death Caesarian section Maternal hypertension Infant respiratory symptom Infant development Adherence Compliance Side effects SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 15

16 First Author, Publication Year, Country, Funding Types and Numbers of Primary Studies Included Population Characteristics Interventions Comparators Clinical Outcomes, Length of Follow-up Follow-up: during pregnancy and up to two years after childbirth MA = meta-analysis; NICU = neonatal intensive care unit; NR = not reported; NRT = nicotine replacement therapy; RCT = randomized controlled trial; SR = systematic review; UK = United Kingdom Table A2: Characteristics of Included Primary Studies First Author, Publication Year, Country, Study Name (if reported), Funding Bradizza et al., USA Funding: National Institute on Drug Abuse and the Office of Research on Women s Health at the National Institute of Health Study Design and Analysis Active-controlled RCT, single center, parallel, 1:1 ratio Analysis: per protocol Sample size calculation: NR Patient Characteristics 70 pregnant smokers with negative affect (i.e., emotional factors including greater anxiety, dysthymia, anger, and stress) Mean age: 25 years Mean gestational age: 15 weeks Average smoking At enrolment: 8 cigarettes per day Interventions Comparators Clinical Outcomes, Length of Follow-up Emotional regulation treatment (ERT)* + CBT for smoking cessation (n=36) *8 sessions: (1) ERT program rationale, introduction to emotions; (2) Dedicated mindfulness practice and mindfulness in daily activities; (3) Preparing for guided imagery/exposure to negative affect smoking situations, mindfulness; (4) Emotions and urges, physiologicallyfocused guided Health and lifestyle intervention (HLS)* + CBT for smoking cessation (n=34) *8 sessions: (1) Benefits of healthy lifestyle; (2) Personal value and priority; (3) Nutrition 1; (4) Nutrition 2; (5) Avoid carbon monoxide poisoning; (6) Reducing HIV risk; (7) Balancing life role; (8) Review of health and lifestyle changes Smoking abstinence rates (biochemically validated) Number of cigarettes smoked per day Follow-up: pre-treatment, 2 months and 4 months post-quit SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 16

17 First Author, Publication Year, Country, Study Name (if reported), Funding Study Design and Analysis Patient Characteristics Interventions Comparators Clinical Outcomes, Length of Follow-up imagery/ exposure to negative affect smoking situations; (5), (6), (7) Mindfulness review; (8) Review of progress Nanovskaya et al., USA Funding: National Institute on Drug Abuse DB, placebocontrolled RCT, single center, parallel, 1:1 ratio Analysis: ITT Sample size calculation: Yes 65 pregnant smokers Mean age: 26.5 years Mean gestational age: 19 weeks Average smoking: Before pregnancy: 18 cigarettes per day At enrolment: 12 cigarettes per day Attempt to quit during pregnancy: 57% Sustained release bupropion (150 mg BID) + behavioral support* (n=30) *35 minute counseling sessions at each of the first 2 visits and 10 minutes of smoking cessation counselling at subsequent visits, delivered by a research nurse using a motivational interview approach Placebo + behavioral support (n=35) Smoking abstinence rates (biochemically validated) Birth and delivery outcomes (birthweight, infant length, head circumference, Apgar score at 5 minutes, ph value of arterial and venous cord blood) Maternal outcomes (BMI at end pf pregnancy, blood pressure, bupropion side effects) Compliance with medication and retention Follow-up: during pregnancy and 6 months postpartum Naughton et al., UK Funding: NIHR Single blinded RCT, multicenter, parallel, 1:1 ratio Analysis: ITT Sample size calculation: Yes 407 pregnant smokers Mean age: 26 years Mean gestational age: 15 weeks Average smoking: Before pregnancy: 16 cigarettes per MiQuit* (n=203) *an automated 12- week advice and support program for quitting smoking in pregnancy delivered by short message service (SMS) text message Usual care (n=204) Smoking abstinence rates (biochemically validated) Follow-up: Abstinence data collected at 4-week follow up and at 36 weeks gestation SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 17

18 First Author, Publication Year, Country, Study Name (if reported), Funding Study Design and Analysis Patient Characteristics Interventions Comparators Clinical Outcomes, Length of Follow-up day At enrolment: 9 cigarettes per day Althabe et al., Argentina Funding: Centers for Disease Control and Prevention Cluster RCT, 1:1 ratio Analysis: ITT Sample size calculation: Yes 3333 pregnant smokers Mean age: 21 years Mean gestational age: NR Counseling* (10 clusters, n=1562) *based on the 5As (Ask, Advise, Assess, Assist, and Arrange) Control (10 clusters; n=1771) Primary outcome Recall receiving 5As Secondary outcomes Continuous smoking Quit smoking during pregnancy Mejdoubi et al., The Netherlands Funding: Netherlands Organization for health Research and Development Single blinded RCT, multicenter, parallel, 1:1 ratio Analysis: per protocol Sample size calculation: NR Percent smoking during pregnancy: 22% 460 pregnant smokers with low education level Mean age: 19 years Mean gestational age: 20 weeks Average smoking: At enrolment: 8 cigarettes per day Attempt to quit during pregnancy: 81% Nurse home visitation* (n=237) *10 home visits during pregnancy, 20 during first year and 20 during the second life year of the child by trained nurses advising how to reduce smoking and how to promote breastfeeding Usual care (n=223) BID = twice daily; BMI = body mass index; DB = double blind; ITT = intention-to-treat; NIHR = National Institute for Health Research; NR = not reported; RCT = randomized controlled trial Follow-up: Baseline, first 48 hours after delivery and during postpartum hospital stay Primary outcome Prevalence of cigarette smoking Percentage of smokers Average number of cigarettes smoked per day Secondary outcomes Birthweight Week of gestation Adverse pregnancy outcomes (low birthweight, prematurity, small gestational age) Breastfeeding initiation Follow-up: Baseline, 32 weeks of pregnancy and two months postpartum SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 18

19 Appendix 3: Quality Assessment of Included Studies Table A3: Quality Assessment of Systematic Reviews SIGN Checklist: Internal Validity 5 1. The research question is clearly defined and the inclusion/exclusion criteria must be listed in the paper Chamberlain et al., Coleman et al., A comprehensive literature search is carried out Yes Yes 3. At least two people should have selected studies Yes Yes 4. At least two people should have extracted data Yes Yes 5. The status of publication was not used as an inclusion criteria Yes Yes 6. The excluded studies are listed Yes Yes 7. The relevant characteristics of the included studies are provided Yes Yes 8. The scientific quality of the included studies was assessed and reported Yes Yes 9. Was the scientific quality of the included studies used appropriately? Yes Yes 10. Appropriate methods are used to combine the individual findings Yes Yes 11. The likelihood of publication bias was assessed appropriately Yes NA 12. Conflicts of interest are declared Yes Yes Overall Assessment of the Study High, Moderate, Low High High For overall assessment of the : High indicated that all or most criteria have been fulfilled; where they have not been fulfilled, the conclusions of the or review are thought very unlikely to alter. Moderate indicates that some of the criteria have been fulfilled; those criteria that have not been fulfilled or not adequately described are thought unlikely to alter the conclusions. Low indicates that few or no criteria fulfilled; the conclusions of the are thought likely or very likely to alter. Yes Yes Table A4: Quality Assessment of Primary Studies SIGN Checklist: Internal Validity 6 1. The addresses an appropriate and clearly focused question. 2. The assignment of subjects to treatment groups is randomized. Bradizza et al., Nanovskaya et al., Naughton et al., Althabe et al., Mejdoubi et al., Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes 3. An adequate concealment method is used. Can t tell Yes Can t tell No Can t tell 4. Subjects and investigators are kept blind about treatment allocation. 5. The treatment and control groups are similar at the start of trial. 6. The only difference between groups is the treatment under investigation. No Yes No No No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 19

20 SIGN Checklist: Internal Validity 6 7. All relevant outcomes are measured in a standard, valid and reliable way. 8. What percentage of the individuals or clusters recruited into each treatment arm of the dropped out before the was completed? 9. All the subjects are analyzed in the groups to which they were randomly allocated (often referred to as intention to treat analysis). 10. Where the is carried out more than one site, results are comparable for all sites. Overall Assessment of the Study Bradizza et al., Nanovskaya et al., Naughton et al., Althabe et al., Mejdoubi et al., Yes Yes Yes Yes Yes Active control (HLS): 44% Intervention (ERT): 53% Placebo: 49% Bupropion SR: 43% Usual care: 19% MiQuit: 13% NR Usual care: 14% Nurse home visit: 4% No Yes No Yes Yes No Yes Yes Yes No High, Moderate, Low Moderate High Moderate Moderate Moderate For overall assessment of the : High indicated that all or most criteria have been fulfilled; where they have not been fulfilled, the conclusions of the or review are thought very unlikely to alter. Moderate indicates that some of the criteria have been fulfilled; those criteria that have not been fulfilled or not adequately described are thought unlikely to alter the conclusions. Low indicates that few or no criteria fulfilled; the conclusions of the are thought likely or very likely to alter. SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 20

21 Appendix 4: Main Study Findings and Author s Conclusions Table A5: Summary of Findings of Included Systematic Reviews Primary outcome: Smoking abstinence in late pregnancy Comparison Main Study Findings No. of Chamberlain et al., RR (95% CI) I 2, % 1) Counselling vs usual care All (1.19 to 1.73) 49 Validated only (1.04 to 1.45) 22 2) Counselling vs less intensive interventions All (1.07 to 1.47) 28 Validated only (1.10 to 1.56) 23 3) Counselling vs alternative interventions (0.86 to 1.53) -- 4) Health education vs usual care All (0.99 to 2.55) 0 Validated only (0.82 to 2.58) 20 5) Health education vs less intensive interventions All (0.85 to 1.70) 33 Validated only (0.70 to 1.91) 52 6) Health education vs alternative (0.19 to 18.60) interventions 7) Feedback vs usual care All (1.89 to 10.21) 0 Validated only (1.38 to 10.93) -- 8) Feedback vs less intensive interventions All (0.75 to 2.20) 0 Validated only (0.75 to 2.20) 0 9) Incentives vs usual care 1 Not estimable 10) Incentives vs less intensive 4 Not pooled 93 interventions 11) Incentives vs alternative interventions All (1.36 to 4.09) 0 Validated only (1.36 to 4.09) 0 12) Social (peer or partner) support vs less intensive interventions All (0.93 to 1.58) 0 Validated only (0.98 to 2.07) 0 13) Exercise vs usual care (0.72 to 2.01) -- Secondary outcomes: Continued abstinence (Relapse prevention) in late pregnancy Comparison No. of RR (95% CI) I 2, % 1) Counselling vs usual care (0.93 to 1.21) 45 2) Counselling vs less intensive interventions (0.99 to 1.13) 0 Author s Conclusions Psychosocial interventions to support women to stop smoking in pregnancy can increase the proportion of women who stop smoking in late pregnancy and the proportion of infants born low birthweight. Counselling, feedback and incentives appear to be effective, however the characteristics and context of the interventions should be carefully considered. The effect of health education and social support is less clear. 7 p.2-3 SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 21

22 Main Study Findings 3) Health education vs usual care (0.86 to 1.23) -- 4) Social (peer or partner) support vs less (0.89 to 1.16) -- intensive interventions Author s Conclusions Continued abstinence in the postnatal period Comparison No. of RR (95% CI) I 2, % 1) Counselling vs usual care 0 to 5 months (1.26 to 2.01) 0 6 to 11 months (1.00 to 1.77) 0 12 to 17 months (1.23 to 3.96) months (0.50 to 1.92) 0 2) Counselling vs less intensive interventions 0 to 5 months (0.93 to 1.43) 23 6 to 11 months (0.91 to 1.31) 0 12 to 17 months (0.87 to 1.41) 26 3) Counselling vs alternative interventions 0 to 5 months (0.63 to 1.76) -- 6 to 11 months (0.33 to 1.73) -- 4) Health education vs usual care 0 to 5 months (1.31 to 9.67) 0 5) Health education vs less intensive interventions 0 to 5 months (1.01 to 2.36) 0 6) Incentives vs usual care 0 to 5 months (0.56 to 2.13) 0 6 to 11 months (2.10 to 7.16) -- 7) Incentives vs less intensive interventions 0 to 5 months (1.54 to 8.58) -- 8) Incentives vs alternative interventions 0 to 5 months (0.57 to 5.61) 52 6 to 11 months (0.85 to 1.01) 0 9) Social (peer or partner) support vs less intensive interventions 0 to 5 months (0.35 to 5.14) 34 6 to 11 months (0.81 to 1.44) 0 12 to 17 months (0.76 to 1.51) -- 10) Exercise vs usual care 6 to 11 months (0.81 to 2.79) -- Smoking reduction in late pregnancy Comparison No. of RR or MD* (95% CI) 1) Counselling vs usual care Validated (0.49 to 1.28) 4 Self-reported (various definition) * (1.27 to 2.17) 0 Decrease in mean cotinine (-0.76 to ) 2) Counselling vs less intensive interventions Validated (0.98 to 1.87) 0 Self-reported >50% reduction (1.07 to 1.71) 0 I 2, % SUMMARY WITH CRITICAL APPRAISAL Smoking Reduction and Cessation Interventions for Pregnant Women and Mothers of Infants 22